Host-targeted Interventions of Category A, B and C Bunyaviruses

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Our project focuses on medically important Category A, B, and C bunyaviruses that cause hemorrhagic fever, cardiopulmonary manifestations, and encephalitis in humans. Most bunyaviruses are arboviruses with a life cycle involving replication in warm-blooded vertebrate species and arthropod vectors in nature. Species central to this proposal include Crimean Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), Sin Nombre virus (SNV), and LaCrosse virus (LACV). These viruses epitomize emerging zoonotic viruses that threaten human populations due to changing geographic and environmental interactions among human and natural reservoirs harboring these viruses. Our project is based on preliminary data indicating that bunyavirus replication physically engages with the cytoplasmic mRNA degradation and related RNA control pathways during replication. We used microarray data to define a set of cellular genes from these control pathways that are similarly up- or down-regulated following infection CCHFV, RVFV, and SNV. The project is organized around two specific aims. Aim 1 is to identify cellular target gene(s) from our restricted starting set of candidate host factors that are required for bunyavirus replication. Such cellular factors would be attractive candidates of high potential for therapeutic intervention. Aim 2 with test the hypothesis that those genes required for bunyavirus replication are necessary for efficient viral transcription or genome replication.